Hydrochloric Acid → 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-(1-ethoxyethylidene) malononitrile (958 mg, 7.04 mmol) in EtOH (12 mL) was added (4-methoxyphenyl)hydrazine (1.12 g, 8.09 mmol). (Prior to using the hydrazine its HCl salt was washed with NaHCO3/CH2Cl2. The organic phase was concentrated and used directly.) The solution was heated to 105° C. in the microwave for 20 minutes. CH2Cl2 was added and the organic phase was washed with 1 M HCl and the organic extract was washed with aqueous NaHCO3. The solution was dried using a phase separator and concentrated under reduced pressure to give 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (1.30 g, 81%) which was used as such in the next step. The procedure was adapted from J. Med. Chem. 2004, 47, 5894-5911.

Provenance & Evidence